Erythropoietine

In orthopaedics, erythropoietin (EPO) is applied in the preoperative management of anaemic patients, but also as a stimulating factor to assist bone regeneration due to its angiogenic and osteoinductive potential. Since orthopaedists mainly rely on their clinical experience to assess bone healing, additional and more objective methods such as studying the dynamics of bone markers are needed. Therefore, the aim of this study was to investigate the plasma activity of bone-specific alkaline phosphatase (BALP), the N-terminal propeptide of type I collagen (PINP), the C-terminal telopeptide of type I collagen (CTX), and deoxypyridinoline (DPD) during the first 2 months of healing of comminuted fractures in cats, either non-stimulated or locally stimulated with recombinant human erythropoietin (rhEPO)...

Congenital Dyserythropoietic Anemia type I (CDA I) is a rare hereditary condition characterized by macrocytic/normocytic anemia, splenomegaly, iron overload, and distinct abnormalities during late erythropoiesis, particularly internuclear bridges between erythroblasts. Diagnosis of CDA I remains challenging due to its rarity, clinical heterogeneity, and overlapping phenotype with other rare hereditary anemias. In this case series, we present 36 patients with suspected CDA I. A molecular diagnosis was successfully established in 89% of cases, identifying 16 patients with CDA I through the presence of 18 causative variants in the CDAN1 or CDIN1 genes...

BACKGROUND: Anemia is associated with adverse outcomes and prolonged hospitalizations in critically ill patients. Regarding the recent adoption of restrictive transfusion protocols in intensive care unit (ICU) management, anemia remains highly prevalent even after ICU discharge. This study aimed to investigate the prevalence of anemia following ICU discharge and factors affecting recovery from anemia. METHODS: In this retrospective cohort study involving 3969 adult ICU survivors, we assessed anemia severity using the National Cancer Institute criteria at six time points: ICU admission, ICU discharge, hospital discharge, and at 3-, 6-, and 12-month post-hospital discharge...

BACKGROUND: Anemia is one of the common complications of chronic kidney disease (CKD), and its prevalence has been arising globally. The key cause of anemia in CKD patients is the diseased kidney's reduced ability to synthesize endogenous erythropoietin (EPO), yet this is not the sole reason. Inflammatory elements, functional iron deficiency, and uremic toxins together participate in the development of anemia. According to research data, anemia is an independent risk factor for cardiovascular events, all-cause mortality, and worsening renal function and affects the clinical prognosis and quality of life of CKD patients...

Sepsis is a life-threatening disease caused by a dysregulated host response to infection, resulting in 11 million deaths globally each year. Vascular endothelial cell dysfunction results in the loss of endothelial barrier integrity, which contributes to sepsis-induced multiple organ failure and mortality. Erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their ephrin ligands play a key role in vascular endothelial barrier disruption but are currently not a therapeutic target in sepsis. Using a cecal ligation and puncture (CLP) mouse model of sepsis, we showed that prophylactic or therapeutic treatment of mice with EphA4-Fc, a decoy receptor and pan-ephrin inhibitor, resulted in improved survival and a reduction in vascular leak, lung injury, and endothelial cell dysfunction...

BACKGROUND: Hypervolemia is thought to be a major contributor to higher left ventricular mass (LVM), a potent predictor for cardiovascular mortality among patients on maintenance hemodialysis. We hypothesized that a decrease in vector length (a bioimpedance proxy of hypervolemia) would be associated with an increase in LVM. METHODS: Using data from the Frequent Hemodialysis Network Daily Trial (n=160) we used linear regression to assess the association of changes in vector length from baseline to month 12 with changes in magnetic resonance imaging (MRI) measures of LVM and other cardiac parameters...

BACKGROUND AND PURPOSE: Our previous study reported that erythroferrone (ERFE), a newly identified hormone produced by erythroblasts, responded to recombinant human erythropoietin (rHuEPO) sensitively but its dynamics was complicated by double peaks and circadian rhythm. This study intends to elucidate the underlying mechanisms for the double peaks of ERFE dynamics and further determine whether early ERFE measurements can predict haemoglobin responses to rHuEPO. EXPERIMENTAL APPROACH: By using the purified recombinant rat ERFE protein and investigating its deposition in rats, the production of ERFE was deconvoluted...

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract. SLC30A10 deficiency results in impaired gastrointestinal manganese excretion, leading to manganese excess, neurologic deficits, liver cirrhosis, polycythemia, and erythropoietin excess. Neurologic and liver disease are attributed to manganese toxicity...

PURPOSE: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. PATIENTS AND METHODS: Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly...

BACKGROUND/AIMS: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. METHODS: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20)...

Olaparib was the first poly ADP-ribose polymerase inhibitor approved for patients with cancer with mutations in either BRCA1 or BRCA2 in China. To the best of our knowledge, however, no study has described the efficacy of olaparib for patients with breast cancer with double mutations in BRCA1 and BRCA2 . The present case report describes a patient with breast cancer with deleterious germline mutations in both BRCA1 and BRCA2 . The 56-year-old patient with multiple metastatic breast cancer underwent breast cancer resection with 12 years interval between removal of the left and right breast...

OBJECTIVES: Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B12 on this toxicity. MATERIALS AND METHODS: A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 μg/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 μg/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment...

BACKGROUND: Increased survival rate of extremely preterm children is associated with a higher risk of retinopathy of prematurity (ROP) and long-term sequelae, which implicate retinal changes. PURPOSE: To assess an influence of perinatal characteristics on morphology and retinal vascularity of the macula in preterm children. METHODS: A cohort of 123 preterm children at the age of 10.5 years (IQR: 8.12-12.77) was prospectively assessed...

Etavopivat is an investigational, once-daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study (https://clinicaltrials.gov/study/NCT03815695) was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: one single-dose; two multiple ascending doses; one open-label [OL]. In the OL cohort, 15 patients (median age 33.0 [range, 17‒55] years received 400-mg etavopivat once daily for 12 weeks; 14 completed treatment...

Inflammation plays a crucial role in the pathophysiology of various kidney diseases. Kidney perivascular cells (pericytes/fibroblasts) are responsible for producing proinflammatory molecules, promoting immune cell infiltration, and enhancing inflammation. Vascular adhesion protein-1, expressed in kidney perivascular cells, is an ectoenzyme that catalyzes the oxidative deamination of primary amines with the production of hydrogen peroxide in the extracellular space. Our study demonstrated that blocking this enzyme suppressed hydrogen peroxide production and neutrophil infiltration, thereby reducing renal ischemia-reperfusion injury...

β-thalassemia is a disorder characterized by anemia, ineffective erythropoiesis (IE), and iron overload, whose treatment still requires improvement. The activin receptor-ligand trap Luspatercept, a novel therapeutic option for β-thalassemia, stimulates erythroid differentiation inhibiting the transforming growth factor β pathway. However, its exact mechanism of action and the possible connection with erythropoietin (Epo), the erythropoiesis governing cytokine, remain to be clarified. Moreover, Luspatercept does not correct all the features of the disease, calling for the identification of strategies that enhance its efficacy...

Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2V617F or several others in exon 12. A 38-year-old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2V617F and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2R715T in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2R715T mutation...

Introduction: Erythropoietin (EPO) acts primarily in regulating red blood cell production mediated by high EPO receptor (EPOR) expression in erythroid progenitor cells. EPO activity in non-erythroid tissue is evident in mice with EPOR restricted to erythroid tissues (ΔEPORE) that become obese, glucose-intolerant, and insulin-resistant. In animal models, nitric oxide synthase (NOS) contributes to EPO activities including erythropoiesis, neuroprotection, and cardioprotection against ischemia-reperfusion injury...

PURPOSE: The purpose of this study is to evaluate the visual response of methanol-induced optic neuropathy to management with erythropoietin (EPO) along with conventional therapy. METHODS: This retrospective case series examines the ophthalmological data of patients diagnosed with methanol-induced optic neuropathy between 2020 and 2021 at two centers, Riyadh, Saudi Arabia. Patients' characteristics and the results of initial and final ophthalmological examinations were documented and compared between patients who received EPO in addition to conventional management and those who received only conventional management...

OBJECTIVE: The aim of this study was to assess the efficacy and safety of a third-generation lentivirus-based vector encoding the feline erythropoietin (EPO) (feEPO) gene in vitro and in rodent models in vivo. This vector incorporates a genetic mechanism to facilitate the termination of the therapeutic effect in the event of supraphysiologic polycythemia, the herpes simplex virus thymidine kinase (HSV-TK) "suicide gene." ANIMALS: CFRK cells and replication-defective lentiviral vectors encoding feEPO were used for in vitro experiments...